Quality Control & Equipments

1. What do you mean by quality?

Answer: Quality is a standard of how good something is as measured against other similar things. According to American Society, quality can be defined in following ways:

1. Based on customers perceptions of product
2. The ability of a product
3. Achieved by conforming to established requirements within an organization

2. What are the criteria of quality?

Answer: The criteria of quality are safety, potency, efficacy, stability, purity, Identify.

3. What is quality control?

Answer: The term quality control refers to the sum of all procedures undertaken to ensure the identity and purity of a particular pharmaceutical. Such procedures may range from the performance of simple chemical experiments which determine the identity and screening for the presence of particular pharmaceutical substance to more complicated requirements of pharmacopoeial monographs.

4. What are the basic requirements of quality control?

Answer:

The basic requirements of quality control are:

1. The finished product container must comply with specification
2. Approved procedure
3. Trained personnel
4. Correct sampling methods
5. Validation testing methods
6. Sufficient retain sample of starting materials, packaging materials and finished materials
7. All batches are reviewed and released by a qualified person to approved procedures
8. Records are kept of all sampling , inspecting and testing procedures
9. Product label check

5. What are the responsibilities of QC department?

Answer:

The responsibilities for QC are as follows:

1. Approve or reject all procedures, specifications, methods, and results.
2. Approve or reject all raw materials, packaging materials, labeling and finished products.
3. Review all production records for accuracy and completeness before approving for distribution.
4. Establish procedures for revising procedures, formulas, etc.
5. Approve changes to procedures, formulas, etc.
6. Ensure that the latest revision is being used at all times.
7. Perform all the required tests to ensure identity, purity, potency and composition, and to ensure that products are not contaminated or adulterated
8. Control of laboratory reagents and equipments
9. Ensure precision and accuracy of all testing methods

6. What is sample?

Answer: Sample is the unit that provides the experimental observations, such as tablet sampled for potency and defects.

7. What is sampling?

Answer: The process of taking a small portion from a batch for test and analysis.

8. What is reference sample?

Answer: A sample of a batch of starting material, packaging material or finished product which is stored for the purpose of being analyzed should the need arise during the shelf life of the batch concerned.

9. What is retention sample ?

Answer:

A sample of a fully packaged unit from a batch of finished product. It is stored for identification purposes. For example, presentation, packaging, labeling, patient information leaflet, batch number, expiry date should the need arise during the shelf life of the batch concerned.

10. What are the major QC instruments?

• HPLC
• GC
• AAS
• FTIR
• UV-visible spectroscopy
• Incubator
• Polarimeter
• Balance
• Autoclave
• PH meter
• Vortex mixer
• Moisture analyzer
• Dissolution tester
• Disintegration tester
• Centrifuge machine
• Conductivity meter
• Friability tester
• Hardness tester
• Electronic heating mantle
• Total organic carbon analyzer
• Tap density meter

11. What is chromatography?

Answer:

Chromatography is a technique to separate mixtures of substances into their components on the basis of their molecular structure and molecular composition. This involves a stationary phase (a solid, or a liquid supported on a solid) and a mobile phase (a liquid or a gas). The mobile phase flows through the stationary phase and carries the components of the mixture with it.

12. What is HPLC?? Write down the types of HPLC.

Answer:

High Performance Liquid Chromatography (HPLC) is a form of column chromatography that pumps a sample mixture or analyte in a solvent (known as the mobile phase) at high pressure through a column with chromatographic packing material (stationary phase).

•Stationary phase : The substance on which adsorption of the analyte (the substance to be separated during chromatography) takes place . It can be a solid, a gel, or a solid liquid combination.

•Mobile phase : Solvent which carries the analyte (a liquid or a gas) 

There are following types of HPLC, depending upon the phase system (stationary) in the process:

Normal Phase HPLC:

This method separates analytes on the basis of polarity. Stationary phase is polar (hydrophilic) and mobile phase is non-polar (hydrophobic).

Reverse Phase HPLC:

It works on the principle of hydrophobic interactions hence the more nonpolar the material is, the longer it will be retained. Stationary phase is non-polar (hydrophobic) and mobile phase is Polar (hydrophilic).

Size-exclusion HPLC:

The column is filled with material having precisely controlled pore sizes, and the particles are separated according to its their molecular size.

Ion-Exchange HPLC:

The stationary phase has an ionically charged surface of opposite charge to the sample ions. This technique is used almost exclusively with ionic or ionizable samples.

BASED ON ELUTION TECHNIQUE

1. Isocratic elution

  •A separation in which the mobile phase composition remains constant throughout the procedure is termed isocratic elution

   •In isocratic elution, peak width increases with retention time linearly with the number of theoretical

plates. This leads to the disadvantage that late-eluting peaks get very flat and broad.

   • Best for simple separations

 • Often used in quality control applications that support and are in close proximity to a manufacturing process

2. Gradient elution

  •A separation in which the mobile phase composition is changed during the separation process is described as a gradient elution

  •Gradient elution decreases the retention of the later-eluting components so that they elute faster, giving narrower peaks . This also improves the peak shape and the peak height

  • Best for the analysis of complex samples

  • Often used in method development for unknown mixtures

  • Linear gradients are most popular

13. Write down the principle of HPLC.

Answer:

HPLC is a technique in analytic chemistry used to separate the components in a mixture , to identify each component and to quantify each component. It relies on pumps to pass a pressurized liquid solvent containing the sample mixture through a column filled with a solid adsorbent material. Each component in the sample interacts slightly different with the adsorbent material causing different flow rates for the different components and leading to the separation of the components as they flow out the column.

14. What are the instrumentation of HPLC?

i. Solvent reservoir

ii. Pump

iii. In line Solvent Filter

iv. Sample injector valve

v. Pre Column Filter                                               

vi. Guard Column

vii. Column

viii. Detector

xi. Data collection devices

15. Write down the pharmaceutical applications and advantages of HPLC?

Answer:

The pharmaceutical applications of HPLC are -

1. To control drug stability.
2. Tablet dissolution study of pharmaceutical dosages form.
3. Pharmaceutical quality control.
4. Shelf life determinations of pharmaceutical products.
5. Identification of counterfeit drug products.

The advantages of HPLC are:

1. The separation becomes faster
2. Very small amount can be detected
3. Sensitive selective detectors
4. Better resolution of compound from the column

16. What is spectrophotometry? What is the basic principle of UV spectrophotometer?

Answer:

Spectrophotometry is the quantitative measurement of the reflection or transmission properties of a material as a function of wavelength. It deals with visible light, near-ultraviolet, and near-infrared, but does not cover time-resolved spectroscopic techniques.

Principle of UV spectrophotometer:

Absorption molecules containing π electrons or non bonding electrons can absorb the energy in the form of ultraviolet or visible light to excite these electrons to higher anti bonding molecular orbitals. The more easily excited the electrons, the longer the wavelength of light it can absorb.

17. What are the instrumentation of UV spectrophotometer?

Answer:

i. Light source

ii. Lens

iii. Monochromator

iv. Wavelength selector

v. Sample solution

vi. Detector

vii. Digital display

18. What is the wavelength of ultraviolet and visible light?

Answer:

The wavelength of ultraviolet light is 185 - 400 nm and visible light is 400 - 700 nm.

19. What is the Lamberts law?

Answer:

 When a monochromatic radiation or light passes through a homogenous transparent medium the rate of decrease of intensity of radiation with the thickness of the absorbing medium is directly proportional to the intensity of the incident light.

20. What is Beers law?

Answer:

When a monochromatic radiation or light passes through a homogenous transparent medium the rate of decrease of intensity of radiation with the concentration of the solute in that system is directly proportional to the intensity of the incident light.

21. What do you mean by Beer-Lamberts s law? Write down the limitations of Beer-Lamberts s law.

Answer:

The Beer Lamberts law states that the absorbance of a solution is directly proportional to the concentration of the absorbing species in the solution and the path length. Thus, for a fixed path length, UV/Vis spectroscopy can be used to determine the concentration of the absorber in a solution. It is necessary to know how the absorbance changes with concentration.

Limitations of Beer-Lamberts s law:

i. Deviations in absorptivity coefficients at high concentrations (>0.01 M)

ii. Interaction with solvent

iii. Changes in refractive index

iv. Shifts in chemical equilibrium

v. Scattering of light due to particulates in the sample

22. What is IR spectroscopy?

Answer:

Infrared spectroscopy is the spectroscopy that deals with the infrared region of the electromagnetic spectrum, that is light with a longer wavelength and lower frequency than visible light. It covers a range of techniques, mostly based on absorption spectroscopy. It uses light over the infrared range 700 - 15000 nm.

23. Write down the theory of IR spectroscopy.

Answer:

IR radiation does not have enough energy to induce electronic transitions as seen with UV. Absorption of IR is restricted to compounds with small energy differences in the possible vibrational and rotational states.

For a molecule to absorb IR, the vibrations or rotations within a molecule must cause a net change in the dipole moment of the molecule. The alternating electrical field of the radiation interacts with fluctuations in the dipole moment of the molecule. If the frequency of the radiation matches the vibrational frequency of the molecule then radiation will be absorbed, causing a change in the amplitude of molecular vibration.

24. What do you mean by FTIR?

Answer:

Fourier Transform Infrared (FTIR) spectroscopy is a measurement technique that allows one to record infrared spectra. Infrared light is guided through an interferometer and then through the sample.

25. What are the instrumentations of FTIR?

Answer:

i. IR source

ii. Half silvered mirror

iii. Fixed mirror

iv. Moving mirror

v. Sample cell

vi. IR sensor

26. What is NMR?

Answer.

Nuclear Magnetic Resonance (NMR) is a process in which nuclei absorb magnetic resonance and re emit electromagnetic radiation. This energy is at a specific resonance frequency which depends on the strength of the magnetic field and the magnetic properties of the isotope of the atoms.

27. Write down the basic principle of NMR.

Answer.

The principle of NMR usually involves two sequential steps:

• The alignment (polarization) of the magnetic nuclear spins in an applied, constant magnetic field B0.
• The perturbation of this alignment of the nuclear spins by employing an electro-magnetic, usually radio frequency (RF) pulse. The required perturbing frequency is dependent upon the static magnetic field (H0) and the nuclei of observation.

The two fields are usually chosen to be perpendicular to each other as this maximizes the NMR signal strength. The resulting response by the total magnetization (M) of the nuclear spins is the phenomenon that is exploited in NMR spectroscopy and magnetic resonance imaging. Both use intense applied magnetic fields (H0) in order to achieve dispersion and very high stability to deliver spectral resolution, the details of which are described by chemical shifts, the Zeeman effect, and Knight shifts (in metals).

NMR phenomena are also utilized in low-field NMR, NMR spectroscopy and MRI in the Earth's magnetic field.

28. What is AAS? What is the basic principle of AAS?

Answer.

Atomic absorption spectroscopy (AAS) is a spectroanalytical procedure for the quantitative determination of chemical elements using the absorption of optical radiation (light) by free atoms in the gaseous state.In analytical chemistry the technique is used for determining the concentration of a particular element (the analyte) in a sample to be analyzed.

Principle of AAS:

The technique makes use of absorption spectrometry to assess the concentration of an analyte in a sample. It requires standards with known analyte content to establish the relation between the measured absorbance and the analyte concentration and relies therefore on the Beer-Lambert Law.

In short, the electrons of the atoms in the atomizer can be promoted to higher orbitals (excited state) for a short period of time (nanoseconds) by absorbing a defined quantity of energy (radiation of a given wavelength). This amount of energy, i.e., wavelength, is specific to a particular electron transition in a particular element. In general, each wavelength corresponds to only one element, and the width of an absorption line is only of the order of a few picometers (pm), which gives the technique its elemental selectivity. The radiation flux without a sample and with a sample in the atomizer is measured using a detector, and the ratio between the two values (the absorbance) is converted to analyte concentration or mass using the Beer-Lambert Law.

29. What is TOC?

Answer.

Total organic carbon (TOC) is the amount of carbon found in an organic compound and is often used as a non-specific indicator of water quality or cleanliness of pharmaceutical manufacturing equipment.

30. What is Karl Fischer titration?

Answer.

Karl Fischer titration is a classic titration method in analytical chemistry that uses coulometric or volumetric titration to determine trace amounts of water in a sample. It was invented in 1935 by the German chemist Karl Fischer.

31. What is chromatography? Write down the types of chromatography.

Answer.

Chromatography is an analytical method by which the compounds are physically separated prior to measurement.

There are four main types of chromatography. These are:

I. Liquid chromatography

II. Gas chromatography

III. Thin layer chromatography and

IV. Paper chromatography

32. What is liquid chromatography?

Answer.

Liquid chromatography is used in the world to test water samples to look for pollution in lakes and rivers. It is used to analyze metal ions and organic compounds in solutions.

33. What is gas chromatography? Write down the principal of gas chromatography.

Answer:

Gas chromatography (GC) is a common type of chromatography used in analytical chemistry for separating and analyzing compounds that can be vaporized without decomposition. Typical uses of GC include testing the purity of a particular substance, or separating the different components of a mixture.

Principle of GC:

Gas chromatography is in principle similar to column chromatography but has several notable differences. First, the process of separating the compounds in a mixture is carried out between a liquid stationary phase and a gas mobile phase, whereas in column chromatography the stationary phase is a solid and the mobile phase is a liquid. Second, the column through which the gas phase passes is located in an oven where the temperature of the gas can be controlled, whereas column chromatography (typically) has no such temperature control. Finally, the concentration of a compound in the gas phase is solely a function of the vapor pressure of the gas.

34. What is thin layer chromatography?

Answer:

Thin-layer chromatography (TLC) is a chromatography technique used to separate non-volatile mixtures. It is performed on a sheet of glass, plastic, or aluminium foil, which is coated with a thin layer of adsorbent material, usually silica gel, aluminium oxide (alumina), or cellulose. This layer of adsorbent is known as the stationary phase.

After the sample has been applied on the plate, a solvent or solvent mixture is drawn up the plate via capillary action. Because different analytes ascend the TLC plate at different rates, separation is achieved.

35. What is Rf value?

Answer: RF value (in chromatography) is the distance travelled by a given component divided by the distance travelled by the solvent front. For a given system at a known temperature, it is a characteristic of the component and can be used to identify components.

36. What is paper chromatography?

Answer: Paper chromatography is an analytical method that is used to separate coloured chemicals or substances.This can also be used in secondary or primary colours in ink experiments. This method has been largely replaced by thin layer chromatography, but is still a powerful teaching tool.

37. What is tablet hardness testing?

Answer:

Tablet hardness testing, is a laboratory technique used by the pharmaceutical industry to test the breaking point and structural integrity of a tablet under conditions of storage, transportation and handling before usage. The breaking point of a tablet is based on its shape. It is similar to friability testing but they are not the same thing.

38. What is friability of tablet and what is the percentage of friability?

Answer:

Friability is the tendency for a tablet to chip, crumble or break following compression. This tendency is normally confined to uncoated tablets and surfaces during handling or subsequent storage.

Percentage of friability =(W1 – W2/W1) × 100

W1 = weight of tablets before testing

W2 = weight of tablets after testing

39. What is friability limit for tablet?

Answer:

According to B.P. percentage of friability should not be more than 0.8%

According to U.S.P. percentage of friability should not be more than 1%

40. Write down the weight variation tolerance for uncoated tablets according to B.P.

Answer:

Average weight of tablets(mg)	Maximum percentage difference allowed
80 or less	10%
80-250	7.5%
More than 250	5%

41. Write down the weight variation tolerance for uncoated tablets according to U.S.P.

Answer:

Average weight of tablets(mg)	Maximum percentage difference allowed
130 or less	10%
130-324	7.5%
More than 324	5%

42. What is disintegration?

Answer:

The process by which a solid oral dosage form breaks up in water measured in a standard apparatus.

43. What is dissolution?

Answer:

Dissolution is the process by which a solid drug substance becomes dissolved in a solvent.

44. What do you mean by moisture content?

Answer:

Moisture content = (weight of water in a sample/weight of dry sample) × 100%

45. What do you mean by LOD?

Answer:

LOD= (weight of water in a sample/total weight of wet sample) × 100%

46. What is calibration?

Answer:

Calibration may be defined as a particular measuring device produce a result within a specified limits by comparison with a reference standard device over an appropriate range of measurements. It is a system of performance checking.

47. What is validation?

Answer:

Validation is a detailed process of conforming that the instrument is installed correctly, that it is operating effectively and that is performing without error. It is a tool to ensure that the analytical method is working well.

48. What is solubility?

Answer:

Solubility is the indicative of maximum concentration that can be dissolved in the solvent to form a saturated solution.